Nephrectomy potentially unnecessary in metastatic kidney cancer

Roshini Claire Anthony
04 Jul 2018
(Photo courtesy of ASCO)

Patients with metastatic clear-cell renal cell carcinoma (mRCC) who received sunitinib appeared to have comparable overall survival (OS) with those who received sunitinib after undergoing cytoreductive nephrectomy, according to the phase III CARMENA* trial.

“Given the many approved options for systemic targeted therapy that are now available, the reassessment of the role of surgery in disease management is important,” said the study authors, led by Professor Arnaud Méjean from the Hôpital Européen Georges-Pompidou in Paris, France.

“Sunitinib alone is non-inferior to cytoreductive nephrectomy followed by sunitinib for OS, both in intermediate- and poor-risk patients with mRCC,” said Méjean. “Cytoreductive nephrectomy should no longer be considered the standard of care in mRCC, at least when medical treatment is required.”

In this multicentre noninferiority trial, 450 adult patients (median age 62 years, 74.7 percent male) with mRCC (no or treated brain metastases) and ECOG performance score 0–1 were randomized to receive sunitinib only (50 mg/day on a 4-week on, 2-week off cycle every 6 weeks; n=224) or cytoreductive nephrectomy followed by sunitinib (initiated 3–6 weeks post-surgery; n=226). At data cut-off, 205 patients in the nephrectomy group had undergone surgery with 176 continuing sunitinib, while 206 patients in the sunitinib only arm were on the drug; this group formed the intention-to-treat population.

After a median 50.9 months, patients on sunitinib alone had longer OS compared with those in the nephrectomy plus sunitinib arm (median, 18.4 vs 13.9 months, hazard ratio [HR], 0.89, 95 percent confidence interval, 0.71–1.10), with an upper margin of ≤1.20 demonstrating non-inferiority of sunitinib only to nephrectomy plus sunitinib. [ASCO 2018, abstract LBA3; N Engl J Med 2018;doi:10.1056/NEJMoa1803675]

The findings were similar regardless of MSKCC** risk profile (median, 23.4 vs 19.0 months, HR, 0.92 for patients with intermediate risk and median, 13.3 vs 10.2 months, HR, 0.86 for patients with poor risk).

Progression-free survival was also longer in patients who received sunitinib only compared with nephrectomy plus sunitinib (median, 8.3 vs 7.2 months, HR, 0.82).

Objective response rate was comparable between patients in the sunitinib only and nephrectomy plus sunitinib arms (29.1 percent vs 27.4 percent), though there was a trend toward greater disease control among patients on sunitinib only (74.6 percent vs 61.8 percent), while clinical benefit, defined as complete or partial response or stable disease for >12 weeks, was greater among patients on sunitinib only (47.9 percent vs 36.6 percent; p=0.02).

Treatment duration was 8.5 and 6.7 months among patients in the sunitinib alone and surgery plus sunitinib arms, respectively, with a similar rate of dose reductions between groups (30.5 and 30.6 percent, respectively). Discontinuation of sunitinib occurred primarily due to disease progression (67.1 percent) and toxicity (13.0 percent).

Grade 3–4 adverse events (AEs) occurred more frequently among patients in the sunitinib only vs nephrectomy plus sunitinib arms (42.7 percent vs 32.8 percent; p=0.04), with asthenia (10 percent vs 9 percent), hand-foot syndrome (6 percent vs 4 percent), anaemia (5 percent vs 3 percent), neutropenia (5 percent vs 3 percent), and urinary tract disorders (4 percent vs 0 percent) the most frequently reported.

According to the researchers, not undergoing nephrectomy may have other benefits for the patients including avoiding surgery-related complications and subsequent surgery, both of which could potentially further delay the initiation of systemic therapy.

They pointed out that as all participants in this study were candidates for nephrectomy, the results may not be applicable to those who are not suitable for surgery such as those with poor performance status. The benefits of nephrectomy may also have been underestimated given the non-inferiority trial design.

According to Drs Robert Motzer and Paul Russo from the Memorial Sloan Kettering Cancer Center in New York City, New York, US, patient selection is key in determining treatment choice.

“We think that nephrectomy in properly chosen patients with metastatic renal cell carcinoma remains an essential component of care,” they said in an editorial. [N Engl J Med 2018;doi:10.1056/NEJMe1806331]

“For practicing surgeons and medical oncologists, these data should not lead to the abandonment of nephrectomy but instead emphasize the importance of careful selection of patients undergoing nephrectomy, on the basis of published risk models,” they said, advocating for identifying patients who would reap the most benefits.


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